Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial

Abstract

Introduction: Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia.

Methods: In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10 weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9 months (1 + 1 co-administration) or YF vaccine administered separately at age 10 months (1 + 1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9 months (3 + 0 separate). Blood samples were collected 28-35 days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres ≥ 1:8 were calculated with 95 % confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than - 10 %.

Results: Forty-eight, 66, and 98 participants enrolled in 3 + 0 separate, 1 + 1 co-administration, and 1 + 1 separate groups respectively had NA results. Per protocol analysis of the 3 + 0 separate, 1 + 1 co-administration, 1 + 1 separate, and the combined 1 + 1 separate and 3 + 0 separate groups found that 81 %, 85 %, 92 %, and 88 % of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1 + 1 co-administration and 1 + 1 separate groups was -7 % (95 % CI, -18 % to 3 %). The difference between 1 + 1 co-administration and 3 + 0 separate groups was 4 % (95 % CI, -10 % to 15 %). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately.

Conclusions: No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9 months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613.

Keywords: Co-administration; Neutralizing antibody titre; Pneumococcal conjugate vaccine; The Gambia; Yellow fever vaccine.

Fig. 1

Trial Profile. Infants aged 0-10 weeks residents in 28 clusters of villages were randomly allocated to receive PCV13 delivered in either a 3+0 or 1+1 schedule. Participants in the 1+1 schedule clusters who were assigned to the measurement of immunogenicity endpoints were randomly allocated to receive either the YF vaccine co-administered at 9 months of age with the PCV booster dose (1+1 PCV/YF co-administration 9-month group) or administered separately at 10 months of age (1+1 PCV/YF separate 10-month group). Blood samples were collected 28-35 days after administration of YF vaccine.

Fig. 2

Non-inferiority analyses of YF virus neutralizing antibody titres in (a) per-protocol and (b) intention to treat analyses.